Packaging system for analyte sensors

ABSTRACT

A system and method are provided for packaging and sterilizing analyte sensors. The packaging system provides a structure for securing the analyte sensors in a fixed position and fixed orientation within the package.

INCORPORATION BY REFERENCE TO RELATED APPLICATIONS

Any and all priority claims identified in the Application Data Sheet, orany correction thereto, are hereby incorporated by reference under 37CFR 1.57. This application is a continuation of U.S. application Ser.No. 14/617,197, filed on Feb. 9, 2015, which claims the benefit of U.S.Provisional Application No. 61/938,614, filed on Feb. 11, 2014. Each ofthe aforementioned applications is incorporated by reference herein inits entirety, and each is hereby expressly made a part of thisspecification.

TECHNICAL FIELD

The embodiments disclosed herein relate to a system and method forpackaging analyte sensors. In particular embodiments, the analytesensors are glucose sensors for use with implantable continuous glucosemonitor systems.

BACKGROUND

Diabetes mellitus is a disorder in which the pancreas cannot createsufficient insulin (Type I or insulin dependent) and/or in which insulinis not effective (Type 2 or non-insulin dependent). In the diabeticstate, the victim suffers from high blood sugar, which can cause anarray of physiological derangements associated with the deterioration ofsmall blood vessels, for example, kidney failure, skin ulcers, orbleeding into the vitreous of the eye. A hypoglycemic reaction (lowblood sugar) can be induced by an inadvertent overdose of insulin, orafter a normal dose of insulin or glucose-lowering agent accompanied byextraordinary exercise or insufficient food intake.

Conventionally, a person with diabetes carries a self-monitoring bloodglucose (SMBG) monitor, which typically requires uncomfortable fingerpricking methods. Due to the lack of comfort and convenience, a personwith diabetes normally only measures his or her glucose levels two tofour times per day. Unfortunately, such time intervals are so far spreadapart that the person with diabetes likely finds out too late of ahyperglycemic or hypoglycemic condition, sometimes incurring dangerousside effects. Glucose levels may be alternatively monitored continuouslyby a sensor system including an on-skin sensor assembly. The sensorsystem may have a wireless transmitter that transmits measurement datato a receiver that processes and displays information based on themeasurements. Such sensor systems are sometimes referred to ascontinuous glucose monitors (CGMs).

Continuous glucose sensors are typically transported by the use ofvarious sterile package systems. One common method for packagingimplantable sensors involves “bagging” the device in a flexible bag.Because the glucose sensors are not secured in fixed positions, thesesensors will often shift and tumble within the package when the packageis moved. Because of susceptibility to movement of sensors within thepackage and because of uneven distribution of radiation emitted todifferent positions within the package, sterilization of glucose sensorstypically requires that the package is subjected to a substantiallyhigher dosage of radiation than what would be required if the glucosesensors were secured to fixed positions within the package. Accordingly,in many instances, the dosage emitted is at a setting such that thedifferent locations of within the package may receive a radiation dosagefrom about 25 kGray to about 35 kGray.

Not only is this a wide range of radiation dosage, but the high overalldosage is required to ensure that the sterilization meets the requiredstandards to account for the possibility that the glucose sensors mayshift to locations within the package that receive a lower dosage ofradiation than other locations that receive a higher dosage ofradiation. Consequently, for various reasons, a glucose sensor thatreceives a higher dosage of radiation (e.g., 35 kGray) may have ashortened sensor lifetime, as compared to a glucose sensor that receivesa lower dosage of radiation (e.g., 25 kGray). For example, a higherdosage of radiation can denature a percentage of the glucose sensor'senzymes used to break down glucose to produce a measured speciesindicative of glucose concentration. Additionally, a higher overalldosage of radiation may also damage the adhesiveness of the adhesivepatch used to adhere an ex vivo portion of a glucose sensor system tothe skin. Furthermore, another drawback to the use of a higher overalldosage of radiation is that potential damage to the package—for example,damage to ink printed on the package/container to provide graphics anddamage to certain contents (e.g., an instruction manual) received by thepackage—becomes more pervasive at high radiation dosages. Heretofore, aseparate package/container was used to hold the glucose sensor duringthe sterilization process. Afterwards, the glucose sensor was taken outof the sterilization package and then placed into a final package whichis then shipped out for use.

Conventionally, the radiation dosage range often used is from about 25kGray to about 35 kGray for implantable glucose sensors. With theproduct advantage of having the products secured in a fixed position andfixed orientation, such that each product receives substantially anequal dosage of the radiation, the higher end of the setting range canbe lowered to reduce the risk of enzyme denaturing. For example, in oneembodiment, the radiation dosage range applied may be from about 25kGray to about 30 kGray. In still another embodiment, lower radiationsetting of the range may be about 10 kGray, 15 kGray, 20 kGray, or 25kGray, and the upper radiation setting of the range may be about 25kGray, 30 kGray, or 35 kGray.

When a package contains a plurality of glucose sensors, and thesesensors are shifted to different positions and/or orientations within apackage prior to or during sterilization, the sensors may each receivedifferent amounts of radiation and a different radiation profile. Thisdifference in radiation dosage may result in inconsistent sensorproperties and thus inconsistent sensor performance among sensors.Accordingly, it is desirable to package the glucose sensors in a mannerthat prevents or substantially minimizes sensor movement within thepackage. It is also desirable to sterilize the glucose sensors in amanner that permits substantial consistency in radiation dosage receivedand substantial consistency in radiation profile.

SUMMARY

The present embodiments have several features, no single one of which issolely responsible for their desirable attributes. Without limiting thescope of the present embodiments as expressed by the claims that follow,their more prominent features will now be discussed briefly. Afterconsidering this discussion, and particularly after reading the sectionentitled “Detailed Description,” one will understand how the features ofthe present embodiments provide the advantages described herein.

In a first aspect, a package is provided for receiving and securing aproduct, the package comprising: a product comprising an implantablecontinuous glucose sensor; at least one first container configured toreceive and secure the product therein; a second container configured toreceive the at least one first container; and a retainer configured tosecure the at least one first container in a fixed position and fixedorientation within the second container such that movement of the secondcontainer does not result in movement of the first container within thesecond container.

In an embodiment of the first aspect, the at least one first containercomprises a plurality of first containers, wherein the at least oneregion of the retainer comprises a plurality of regions each configuredto secure one of the plurality of first containers.

In an embodiment of the first aspect, the plurality of regions of theretainer are spaced apart at an equal distance such that the pluralityof first containers are spaced apart at an equal distance.

In an embodiment of the first aspect, the plurality of products arealigned in a uniform orientation.

In an embodiment of the first aspect, the retainer is an integralcomponent of the second container.

In an embodiment of the first aspect, the retainer is an insertreleasably attached to the second container.

In an embodiment of the first aspect, the region of the retainercomprises an aperture or pocket shaped to receive and conform to aregion of the first container.

In an embodiment of the first aspect, the product further comprises ahousing configured to receive an electronics unit, wherein the housingcomprises an adhesive configured to attach the housing to the host.

In an embodiment of the first aspect, the product further comprises aninsertion device configured to insert the implantable continuous glucosesensor into the host.

In an embodiment of the first aspect, the first container comprises ashaped layer and a backing layer adhered to the shaped layer.

In an embodiment of the first aspect, the backing layer comprises amaterial selected from the group consisting of: polyvinyl chloride,polyvinylidenechloride, polyacrylonitrile, polyethylene, polyethyleneterephthalate, polyethylene naphthalate, polypropylene, polyacrylate,cyclic olefins, polystyrene, polyesters, polyamides, ethylene vinylalcohol, polyvinyl alcohol, and copolymers thereof; and paper.

In an embodiment the first aspect, the shaped layer is a molded partwith a chamber for receiving the product.

In an embodiment of the first aspect, the shaped layer is formed of afilm.

In an embodiment of the first aspect, the film comprises a polymerselected from the group consisting of: polyvinyl chloride, polyethylene,polyethylene terephthalate, polyethylene terephthalate glycol,polyvinylidene chloride, polypropylene, polyethylene, styrene, andcopolymers thereof.

In an embodiment of the first aspect, the shaped layer comprises atleast one region configured to secure the product in a fixed positionand fixed orientation within the at least one first container such thatmovement of the at least one first container and/or the second containerdoes not result in movement of the product within the at least one firstcontainer.

In an embodiment of the first aspect, the at least one region of theshaped layer comprises a plurality of regions configured to secure theproduct in a fixed position and fixed orientation within the at leastone first container.

In an embodiment of the first aspect, the shaped layer is shaped anddimensioned to prevent bending of the adhesive patch.

In an embodiment of the first aspect, the product further comprises athird container, wherein the third container is dimensioned andconfigured to receive a plurality of second containers and secure theplurality of second containers in a fixed position and fixedorientation.

In an embodiment of the first aspect, the third container is dimensionedand configured to hold only one level of a plurality of secondcontainers.

Any of the aforementioned embodiments of the first aspect can becombined with one or more other embodiments of the first aspect.

In a second aspect, a method is provided for sterilizing a product, themethod comprising: securing a product in a fixed position and fixedorientation within a first container such that movement of the firstcontainer does not result in movement or orientation change of theproduct within the first container, wherein the product comprises animplantable continuous glucose sensor; repeating securing a product in afirst container; securing a plurality of first containers in a fixedposition and fixed orientation within the second container such that aplurality of products are in a uniform orientation and such thatmovement of the second container does not result in movement ororientation change of the plurality of products within the secondcontainer; moving the second container to a sterilization apparatus; andsterilizing the plurality of products such that each of the plurality ofproducts receive an equal dose of radiation.

In an embodiment of the second aspect, moving the second container isperformed by a conveyor system.

In an embodiment of the second aspect, sterilizing is performed bylight-based sterilization.

In an embodiment of the second aspect, securing a product is performedby securing the product in a shaped layer and attaching a backing layerto the shaped layer to create a seal.

In an embodiment of the second aspect, the shaped layer is a molded partwith a chamber for receiving the product.

In an embodiment of the second aspect, the shaped layer is formed of afilm.

In an embodiment of the second aspect, the film comprises a polymerselected from the group consisting of: polyvinyl chloride, polyethylene,polyethylene terephthalate, polyethylene terephthalate glycol,polyvinylidene chloride, polypropylene, polyethylene, styrene, andcopolymers thereof.

In an embodiment of the second aspect, the shaped layer comprises atleast one region configured to secure the product in a fixed positionand fixed orientation within the at least one first container such thatmovement of the first container and/or the second container does notresult in movement of the product within the first container.

In an embodiment of the second aspect, the product comprises animplantable continuous glucose sensor and a housing configured toreceive an electronics unit, wherein the housing comprises an adhesivepatch configured to attach the housing to the host.

In an embodiment of the second aspect, the shaped layer is shaped anddimensioned to prevent bending of the adhesive patch.

In an embodiment of the second aspect, securing a plurality of firstcontainers in a fixed position and fixed orientation within the secondcontainer is performed by aligning and affixing a region of the firstcontainer to a retainer.

In an embodiment of the second aspect, the retainer comprises anaperture or pocket shaped to receive and conform to the region of thefirst container.

In an embodiment of the second aspect, the method further comprisessecuring a plurality of second containers in a fixed position and fixedorientation within a third container such that a plurality of productsare in a uniform orientation and such that movement of the thirdcontainer does not result in movement or orientation change of theplurality of products within the second container and the firstcontainer.

In an embodiment of the second aspect, the method further comprisesmoving the third container to a sterilization apparatus; and sterilizingthe plurality of products such that each of the plurality of productsreceive an equal dose of radiation.

In an embodiment of the second aspect, the third container isdimensioned and configured to hold only one level of a plurality ofsecond containers.

Any of the aforementioned embodiments of the second aspect can becombined with one or more other embodiments of the second aspect.

In a third aspect, a kit is provided comprising: a product comprising animplantable glucose sensor; at least one first container configured toreceive and secure the product therein; a second container configured toreceive the at least one first container; and a retainer comprising atleast one a region configured to secure the at least one first containerin a fixed position and fixed orientation within the second containersuch that movement of the second container does not result in movementof the first container within the second container.

In an embodiment of the third aspect, the product further comprises ahousing configured to receive an electronics unit, wherein the housingcomprises an adhesive configured to attach the housing to the host.

In an embodiment of the third aspect, the product further comprises aninsertion device configured to insert the implantable glucose sensorinto a host.

Any of the aforementioned embodiments of the third aspect can becombined with one or more other embodiments of the third aspect.

The method of the second aspect and the various embodiments thereof canbe combined with the package of the first aspect and the variousembodiments thereof and/or the kit of the third aspect and the variousembodiments thereof. Similarly, the package of the first aspect can becombined with the kit of the third aspect.

BRIEF DESCRIPTION OF THE DRAWINGS

The present embodiments have several features, no single one of which issolely responsible for their desirable attributes. Without limiting thescope of the present embodiments as expressed by the claims that follow,their more prominent features now will be discussed briefly. Afterconsidering this discussion, and particularly after reading the sectionentitled “Detailed Description,” one will understand how the features ofthe present embodiments provide the advantages described herein.

FIG. 1 is a schematic view of one embodiment of a continuous analytesensor system attached to a host and communicating with other devices;

FIG. 2 is an exploded perspective view of one embodiment of atranscutaneous sensor system.

FIG. 3A is a perspective view of one embodiment a sensor insertiondevice.

FIG. 3B is a perspective view of another embodiment of a sensorinsertion device.

FIG. 3C is a close-up view of a portion of the embodiment illustrated inFIG. 3B.

FIG. 3D is another perspective view of the embodiment illustrated inFIG. 3B.

FIG. 3E is a close-up view of a portion of the embodiment illustrated inFIG. 3D.

FIG. 4A is an exploded perspective view of one embodiment of a packagingsystem.

FIG. 4B is a perspective view of the embodiment shown in FIG. 4A, afterthe retainer and protective packages have been placed into the secondarycontainer.

FIG. 4C is a perspective view of another embodiment of a packagingsystem, after the retainer and a protective package have been placedinto the secondary container.

FIG. 5A is a an exploded view of a protective package configured toreceive a product comprising an implantable continuous glucose sensor,an on-skin housing configured to receive an electronics unit operativelyconnected to the sensor, and a sensor insertion device.

FIG. 5B is a perspective view of a medical device product placed into ashaped layer.

FIG. 5C is a perspective view of the protective package of FIG. 5A afterit has been assembled and sealed.

FIG. 6 is a perspective view of a retainer configured to secureprotective packages (and the products received therein) in fixedpositions within the second container.

FIG. 7 is a flowchart illustrating an embodiment of a method forpackaging and sterilizing a medical device.

FIG. 8 is a perspective view illustrating one embodiment of aninteractive packaging system.

DETAILED DESCRIPTION

The following detailed description describes the present embodimentswith reference to the drawings. In the drawings, reference numbers labelelements of the present embodiments. These reference numbers arereproduced below in connection with the discussion of the correspondingdrawing features. Dimensions of certain parts shown in the drawings mayhave been modified and/or exaggerated for the purposes of clarity orillustration.

The present embodiments are described below with reference to thefigures. These figures, and their written descriptions, may indicatethat certain components of the apparatus are formed integrally, andcertain other components are formed as separate pieces. Those ofordinary skill in the art will appreciate that components shown anddescribed herein as being formed integrally may in alternativeembodiments be formed as separate pieces. Those of ordinary skill in theart will further appreciate that components shown and described hereinas being formed as separate pieces may in alternative embodiments beformed integrally. Further, as used herein the term integral describes asingle unitary piece.

Continuous Analyte Monitoring System

For illustrative purposes, reference will now be made to FIG. 1, whichis an example environment in which some embodiments described herein maybe implemented. Here, an analyte monitoring system 100 includes acontinuous analyte sensor system 108. Continuous analyte sensor system108 includes a sensor electronics module 112 and a continuous analytesensor 110. The system 100 can also include other devices and/orsensors, such as a medicament delivery pump 102 and a reference analytemeter 104, as illustrated in FIG. 1. The continuous analyte sensor 110may be physically connected to sensor electronics module 112 and may beintegral with (e.g., non-releasably attached to) or releasablyattachable to the continuous analyte sensor 10. Alternatively, thecontinuous analyte sensor 110 may be physically separate to sensorelectronics module 112, but electronically coupled via inductivecoupling or the like. Further, the sensor electronics module 112,medicament delivery pump 102, and/or analyte reference meter 104 maycommunicate with one or more additional devices, such as any or all ofdisplay devices 114, 116, 118, 120, and 121.

The system 100 of FIG. 1 also includes a cloud-based processor 122configured to analyze analyte data, medicament delivery data, and/orother patient related data provided over network 124 directly orindirectly from one or more of sensor system 108, medicament deliverypump 102, reference analyte meter 104, and display devices 114-121.Based on the received data, the processor 122 can further process thedata, generate reports providing statistic based on the processed data,trigger notifications to electronic devices associated with the host orcaretaker of the host, or provide processed information to any of theother devices of FIG. 1. In some example implementations, thecloud-based processor 122 comprises one or more servers. If thecloud-based processor 122 comprises multiple servers, the servers can beeither geographically local or separate from one another. The network124 can include any wired and wireless communication medium to transmitdata, including WiFi networks, cellular networks, the Internet and anycombinations thereof.

It should be understood that although the example implementationdescribed with respect to FIG. 1 refers to analyte data being receivedby processor 122, other types of data processed and raw data may bereceived as well.

In some example implementations, the sensor electronics module 112 mayinclude electronic circuitry associated with measuring and processingdata generated by the continuous analyte sensor 110. This generatedcontinuous analyte sensor data may also include algorithms, which can beused to process and calibrate the continuous analyte sensor data,although these algorithms may be provided in other ways as well. Thesensor electronics module 112 may include hardware, firmware, software,or a combination thereof to provide measurement of levels of the analytevia a continuous analyte sensor, such as a continuous glucose sensor.

The sensor electronics module 112 may, as noted, couple (e.g.,wirelessly and the like) with one or more devices, such as any or all ofdisplay devices 114, 116, 118, 120, and 121. The display devices 114,116, 118, 120, and/or 121 may be configured for processing andpresenting information, such sensor information transmitted by thesensor electronics module 112 for display at the display device. Thedisplay devices 14, 16, 18, 20, and 21 can also trigger alarms based onthe analyte sensor data.

In FIG. 1, display device 114 is a key fob-like display device, displaydevice 16 is a hand-held application-specific computing device 116(e.g., the Dexcom G4® Platinum receiver commercially available fromDexcom, Inc.), display device 18 is a general purpose smart phone ortablet computing device 120 (e.g., an Apple® iPhone®, iPad®, or iPodTouch® commercially available from Apple, Inc.), display device 120 is acomputer workstation 120, and display device 121 is any wearable. Insome example implementations, the relatively small, key fob-like displaydevice 114 may be a computing device embodied in a wrist watch, a belt,a necklace, a pendent, a piece of jewelry, an adhesive patch, a pager, akey fob, a plastic card (e.g., credit card), an identification (ID)card, and/or the like. This small display device 114 may include arelatively small display (e.g., smaller than the display device 118) andmay be configured to display a limited set of displayable sensorinformation, such as a numerical value 126 and/or an arrow 128. Incontrast, display devices 116, 118, and 120 can be larger displaydevices that can be capable of displaying a larger set of displayableinformation, such as a trend graph 130 depicted on the hand-heldreceiver 116 in addition to other information such as a numerical valueand arrow.

It is understood that any other user equipment (e.g., computing devices)configured to at least present information (e.g., a medicament deliveryinformation, discrete self-monitoring analyte readings, heart ratemonitor, caloric intake monitor, and the like) can be used in additionor instead of those discussed with reference to FIG. 1.

In some example implementations of FIG. 1, the continuous analyte sensor110 comprises a sensor for detecting and/or measuring analytes, and thecontinuous analyte sensor 110 may be configured to continuously detectand/or measure analytes as a non-invasive device, a subcutaneous device,a transdermal device, and/or an intravascular device. In some exampleimplementations, the continuous analyte sensor 110 may analyze aplurality of intermittent blood samples, although other analytes may beused as well.

In some example implementations of FIG. 1, the continuous analyte sensor110 may comprise a glucose sensor configured to measure glucose in theblood using one or more measurement techniques, such as enzymatic,chemical, physical, electrochemical, spectrophotometric, polarimetric,calorimetric, iontophoretic, radiometric, immunochemical, and the like.In implementations in which the continuous analyte sensor 110 includes aglucose sensor, the glucose sensor may comprise any device capable ofmeasuring the concentration of glucose and may use a variety oftechniques to measure glucose including invasive, minimally invasive,and non-invasive sensing techniques (e.g., fluorescent monitoring), toprovide a data, such as a data stream, indicative of the concentrationof glucose in a host. The data stream may be raw data signal, which isconverted into a calibrated and/or filtered data stream used to providea value of glucose to a host, such as a user, a patient, or a caretaker(e.g., a parent, a relative, a guardian, a teacher, a doctor, a nurse,or any other individual that has an interest in the wellbeing of thehost). Moreover, the continuous analyte sensor 110 may be implanted asat least one of the following types of sensors: an implantable glucosesensor, a transcutaneous glucose sensor, implanted in a host vessel orextracorporeally, a subcutaneous sensor, a refillable subcutaneoussensor, an intravascular sensor.

In some implementations of FIG. 1, the continuous analyte sensor system8 includes a Dexcom G4® Platinum glucose sensor and transmittercommercially available from Dexcom, Inc., for continuously monitoring ahost's glucose levels.

Sensor System

The preferred embodiments relate to the use of an analyte sensor thatmeasures a concentration of glucose or a substance indicative of theconcentration or presence of the analyte. In some embodiments, theanalyte sensor is a continuous device, for example a subcutaneous,transdermal, transcutaneous, and/or intravascular (e.g., intravenous)device. In some embodiments, the device can analyze a plurality ofintermittent blood samples. The analyte sensor can use any method ofglucose-measurement, including enzymatic, chemical, physical,electrochemical, optical, optochemical, fluorescence-based,spectrophotometric, spectroscopic (e.g., optical absorptionspectroscopy, Raman spectroscopy, etc.), polarimetric, calorimetric,iontophoretic, radiometric, and the like.

The analyte sensor can use any known method, including invasive,minimally invasive, and non-invasive sensing techniques, to provide adata stream indicative of the concentration of the analyte in a host.The data stream is typically a raw data signal that is used to provide auseful value of the analyte to a user, such as a patient or health careprofessional (e.g., doctor), who may be using the sensor.

Although much of the description and examples are drawn to a glucosesensor, the systems and methods of the preferred embodiments can beapplied to any measurable analyte. In some preferred embodiments, theanalyte sensor is a glucose sensor capable of measuring theconcentration of glucose in a host. One example embodiment is describedbelow, which utilizes an implantable glucose sensor. However, it shouldbe understood that the devices and methods described herein can beapplied to any device capable of detecting a concentration of analyteand providing an output signal that represents the concentration of theanalyte.

In one preferred embodiment, the analyte sensor is a wholly implantableglucose sensor, such as described with reference to U.S. Pat. No.6,001,067 and U.S. Patent Publication No. US-2011-0027127-A1. In anotherpreferred embodiment, the analyte sensor is a transcutaneous glucosesensor, such as described with reference to U.S. Patent Publication No.US-2006-0020187-A1. In yet another preferred embodiment, the analytesensor is a dual electrode analyte sensor, such as described withreference to U.S. Patent Publication No. US-2009-0137887-A1. In stillother embodiments, the sensor is configured to be implanted in a hostvessel or extracorporeally, such as is described in U.S. PatentPublication No. US-2007-0027385-A1.

The term “analyte” as used herein is a broad term, and is to be givenits ordinary and customary meaning to a person of ordinary skill in theart (and it is not to be limited to a special or customized meaning),and refers without limitation to a substance or chemical constituent ina biological fluid (for example, blood, interstitial fluid, cerebralspinal fluid, lymph fluid or urine) that can be analyzed. Analytes mayinclude naturally occurring substances, artificial substances,metabolites, and/or reaction products. In some embodiments, the analytefor measurement by the sensor heads, devices, and methods disclosedherein is glucose. However, other analytes are contemplated as well,including but not limited to lactate or lactic acid; cardiac markers;ketone bodies; acetone; acetoacetic acid; beta hydroxybutyric acid;glucagon, acetyl Co A; intermediaries in the Citric Acid Cycle; choline,testosterone; creatinine; triglycerides; sodium; potassium; chloride;bicarbonate; total protein; alkaline phosphatase; calcium; phosphorus;PO₂; PCO₂; bilirubin (direct and total); red blood cell count; whiteblood cell count; hemoglobin; hemactocrit; lymphocytes; monocytes;eosinophils; basophils; c-reactive protein; cryoglobulins; fibrinogens;ACTH; aldosterone; ammonia; beta-HCG; magnesium; copper; iron; totalcholesterol; low density lipoproteins; high density lipoproteins;lipoprotein A; T4 (total and free); TSH; FSH; LH; ACTH; hepatitis BEantigen; hepatitis B surface antigen; hepatitis A antibody; hepatitis Cantibody; acarboxyprothrombin; acylcarnitine; adenine phosphoribosyltransferase; adenosine deaminase; albumin; alpha-fetoprotein; amino acidprofiles (arginine (Krebs cycle), histidine/urocanic acid, homocysteine,phenylalanine/tyrosine, tryptophan); andrenostenedione; antipyrine;arabinitol enantiomers; arginase; benzoylecgonine (cocaine);biotinidase; biopterin; c-reactive protein; carnitine; carnosinase; CD4;ceruloplasmin; chenodeoxycholic acid; chloroquine; cholesterol;cholinesterase; conjugated 1-β hydroxy-cholic acid; cortisol; creatinekinase; creatine kinase MM isoenzyme; cyclosporin A; d-penicillamine;de-ethylchloroquine; dehydroepiandrosterone sulfate; DNA (acetylatorpolymorphism, alcohol dehydrogenase, alpha 1-antitrypsin, cysticfibrosis, Duchenne/Becker muscular dystrophy, analyte-6-phosphatedehydrogenase, hemoglobinopathies A, S, C, and E, D-Punjab,beta-thalassemia, hepatitis B virus, HCMV, HIV-1, HTLV-1, Leberhereditary optic neuropathy, MCAD, RNA, PKU, Plasmodium vivax, sexualdifferentiation, 21-deoxycortisol); desbutylhalofantrine;dihydropteridine reductase; diptheria/tetanus antitoxin; erythrocytearginase; erythrocyte protoporphyrin; esterase D; fattyacids/acylglycines; free β-human chorionic gonadotropin; freeerythrocyte porphyrin; free thyroxine (FT4); free tri-iodothyronine(FT3); fumarylacetoacetase; galactose/gal-1-phosphate;galactose-1-phosphate uridyltransferase; gentamicin; analyte-6-phosphatedehydrogenase; glutathione; glutathione perioxidase; glycocholic acid;glycosylated hemoglobin; halofantrine; hemoglobin variants;hexosaminidase A; human erythrocyte carbonic anhydrase I; 17alpha-hydroxyprogesterone; hypoxanthine phosphoribosyl transferase;immunoreactive trypsin; lactate; lead; lipoproteins ((a), B/A-1, β);lysozyme; mefloquine; netilmicin; phenobarbitone; phenytoin;phytanic/pristanic acid; progesterone; prolactin; prolidase; purinenucleoside phosphorylase; quinine; reverse tri-iodothyronine (rT3);selenium; serum pancreatic lipase; sissomicin; somatomedin C; specificantibodies (adenovirus, anti-nuclear antibody, anti-zeta antibody,arbovirus, Aujeszky's disease virus, dengue virus, Dracunculusmedinensis, Echinococcus granulosus, Entamoeba histolytica, enterovirus,Giardia duodenalisa, Helicobacter pylori, hepatitis B virus, herpesvirus, HIV-1, IgE (atopic disease), influenza virus, Leishmaniadonovani, leptospira, measles/mumps/rubella, Mycobacterium leprae,Mycoplasma pneumoniae, Myoglobin, Onchocerca volvulus, parainfluenzavirus, Plasmodium falciparum, poliovirus, Pseudomonas aeruginosa,respiratory syncytial virus, rickettsia (scrub typhus), Schistosomamansoni, Toxoplasma gondii, Trepenoma pallidium, Trypanosomacruzi/rangeli, vesicular stomatis virus, Wuchereria bancrofti, yellowfever virus); specific antigens (hepatitis B virus, HIV-1);succinylacetone; sulfadoxine; theophylline; thyrotropin (TSH); thyroxine(T4); thyroxine-binding globulin; trace elements; transferrin;UDP-galactose-4-epimerase; urea; uroporphyrinogen I synthase; vitamin A;white blood cells; and zinc protoporphyrin. Salts, sugar, protein, fat,vitamins, and hormones naturally occurring in blood or interstitialfluids may also constitute analytes in certain embodiments. The analytemay be naturally present in the biological fluid, for example, ametabolic product, a hormone, an antigen, an antibody, and the like.Alternatively, the analyte may be introduced into the body, for example,a contrast agent for imaging, a radioisotope, a chemical agent, afluorocarbon-based synthetic blood, or a drug or pharmaceuticalcomposition, including but not limited to insulin; ethanol; cannabis(marijuana, tetrahydrocannabinol, hashish); inhalants (nitrous oxide,amyl nitrite, butyl nitrite, chlorohydrocarbons, hydrocarbons); cocaine(crack cocaine); stimulants (amphetamines, methamphetamines, Ritalin,Cylert, Preludin, Didrex, PreState, Voranil, Sandrex, Plegine);depressants (barbituates, methaqualone, tranquilizers such as Valium,Librium, Miltown, Serax, Equanil, Tranxene); hallucinogens(phencyclidine, lysergic acid, mescaline, peyote, psilocybin); narcotics(heroin, codeine, morphine, opium, meperidine, Percocet, Percodan,Tussionex, Fentanyl, Darvon, Talwin, Lomotil); designer drugs (analogsof fentanyl, meperidine, amphetamines, methamphetamines, andphencyclidine, for example, Ecstasy); anabolic steroids; and nicotine.The metabolic products of drugs and pharmaceutical compositions are alsocontemplated analytes. Analytes such as neurochemicals and otherchemicals generated within the body may also be analyzed, such as, forexample, ascorbic acid, uric acid, dopamine, noradrenaline,3-methoxytyramine (3MT), 3,4-dihydroxyphenylacetic acid (DOPAC),homovanillic acid (HVA), 5-hydroxytryptamine (5HT), and5-hydroxyindoleacetic acid (FHIAA).

FIG. 2 illustrates an exploded perspective view of a transcutaneoussensor system 200. In this particular embodiment, the sensor 210 isoperably attached to an on-skin electronics housing unit 214, alsoreferred to as a housing 214, configured to receive electronics 216. Thehousing 214 comprises a base 224 adapted for fastening to a host's skin.The base 224 can be formed from a variety of hard or soft materials, andpreferably comprises a low profile for minimizing protrusion of thedevice from the host during use. In some embodiments, the base 224 isformed at least partially from a flexible material, which is believed toprovide numerous advantages over conventional transcutaneous sensors,which, unfortunately, can suffer from motion-related artifactsassociated with the host's movement when the host is using the device.For example, when a transcutaneous analyte sensor 210 is inserted intothe host, various movements of the sensor 210 (for example, relativemovement between the in vivo portion and the ex vivo portion, movementof the skin, and/or movement within the host (dermis or subcutaneous))create stresses on the device and can produce noise in the sensorsignal. It is believed that even small movements of the skin cantranslate to discomfort and/or motion-related artifact, which can bereduced or obviated by a flexible or articulated base. Thus, byproviding flexibility and/or articulation of the device against thehost's skin, better conformity of the sensor system to the regular useand movements of the host can be achieved. Flexibility or articulationis believed to increase adhesion (with the use of an adhesive pad orpatch) of the electronics housing unit onto the skin, thereby decreasingmotion-related artifact that can otherwise translate from the host'smovements and reduced sensor performance.

The process of applying the sensor to the person is important for such asystem to be effective and user friendly. The application process shouldresult in the sensor assembly being attached to the person in a statewhere it is capable of sensing glucose level information, communicatingthe glucose level information to the transmitter, and transmitting theglucose level information to the receiver.

In some embodiments, such as the embodiments illustrated in FIGS. 3A and3B, the sensor insertion device 310, 320 may employ an automatic,semi-automatic, or manual mechanism for implanting a sensor in a host.The expression “sensor insertion device” as used herein is a broad term,and is to be given its ordinary and customary meaning to a person ofordinary skill in the art (and it is not to be limited to a special orcustomized meaning), and refers without limitation to a devicecomprising a sensor insertion mechanism employed to insert a sensor intoa host.

In one embodiment, as illustrated in FIG. 3A, the sensor insertiondevice 310 includes a base configured to secure a housing (not shown)configured to receive an electronics unit (not shown) configured togenerate analyte information based on a signal from a sensor. The sensorinsertion device 310 also includes a sensor insertion mechanism (notshown) configured to insert the sensor into the host and a trigger 314configured (in response to activation) to cause the sensor insertionmechanism to insert the sensor into the host and to cause the housing todetach from the base. In one embodiment, the sensor mechanism isconfigured, in response to the activation of the trigger 314, to rotatea component (e.g., a wheel) in response to a torque from the torsionspring, whereby a needle is caused to be inserted into the host and tobe retracted from the host thereafter.

In another embodiment, as illustrated in FIGS. 3B and 3D, the sensorinsertion device 320 employs a substantially manual mechanism for sensorinsertion. The sensor insertion device 320 includes an insertion devicebody that aides in aligning and guiding the insertion device components.Preferably, the insertion device body includes an insertion device bodybase that engages an on-skin housing 324 configured to receive anelectronics unit. The sensor insertion mechanism comprises a guide tubesubassembly that includes a guide tube carrier and a guide tube (bothnot shown). In some embodiments, the guide tube is a cannula. The guidetube carrier slides along the insertion device body and maintains theappropriate relative position of the guide tube during sensor insertionand subsequent retraction of the guide tube. The insertion device 320also includes a plunger subassembly comprising a plunger and plungercap. The plunger subassembly cooperates with other insertion devicecomponents to ensure proper insertion and subsequent retraction of theinsertion device components. As illustrated in FIGS. 3B and 3D and asdescribed in the Packaging System section, in some embodiments, thesensor insertion device may comprise one or more notches, 372, 374 thatare configured to securely engage one or more portions of a protectivepackage. Close-up views of these notches are illustrated in FIGS. 3C and3E. The above-described engagement helps secure the sensor insertiondevice and any other components attached thereto to the protectivepackage, such that movement of the protective package does not result ina shift in the position or orientation of the sensor insertion devicerelative to the protective package.

Packaging System

As described elsewhere herein, conventional techniques for packagingimplantable glucose sensors typically involves placing one or moresensors in a flexible bag wherein the sensors are not secured in a fixedposition and fixed orientation. Consequently, the sensors packaged usingthese techniques will often shift and tumble within the package duringmovement of the package. In preferred embodiments described herein, apackaging system is provided that provides a mechanism for securing thesensors in a manner that prevents sensor movement within the package.

The preferred embodiments relate to the use of a packaging system thatreceives a medical device product prior to, during, and aftersterilization. The term “product” as used herein is a broad term, and isto be given its ordinary and customary meaning to a person of ordinaryskill in the art (and it is not to be limited to a special or customizedmeaning), and refers without limitation to a medical device that isdesigned to be received by a container or package. In certainembodiments, the product being packaged may comprise any of a variety ofsensor insertion devices and/or analyte sensors. For example, in oneembodiment, the product may consist only of an implantable continuousglucose sensor. In another embodiment, the product may include anon-skin sensor assembly comprising an implantable continuous glucosesensor and a housing configured to receive an electronics unitoperatively connected to the sensor. In still another embodiment, theproduct may include the above-described on-skin assembly (comprising theimplantable continuous glucose and the housing) and any of a variety ofsensor insertion devices configured to insert the sensor into the host.

FIG. 4A shows an exploded perspective view one embodiment of a packagesystem 400 for packaging a plurality of medical device products. Thepackage system 400 includes a secondary container 410 that receives atleast one protective package or container 420. In turn, as illustratedin FIG. 5A-5C, each protective package 420, 520 receives at least onemedical device product. The package system 400 may also include aretainer 430 designed to secure the protective package(s) 420 in a fixedposition and fixed orientation within the secondary container 410, suchthat movement of the secondary container 410 will not likely result inmovement of the protective package 420 within the secondary container410. FIG. 4B illustrates a perspective view of the embodiment shown inFIG. 4A after the retainer 430 and protective packages 420 have beenplaced into the secondary container 410. In should be understood thatalthough the in the embodiments described with reference to FIGS. 4A and4B, the packaging system 400 is designed to hold and secure fourproducts, in other embodiments, the packaging system 400 may be designedto hold any of a number of products, such as two, three, five, six,nine, ten, twelve, sixteen, twenty or more products. For example, asillustrated in FIG. 4C, in one embodiment, the packaging system 400 isdesigned to hold one protective package with a product therein.

Referring to FIG. 5A, which provides an exploded view, the protectivepackage 520 may be formed of a shaped layer 540 sealed (or otherwisebonded) to a backing layer 542. The shaped layer 540 has a compartment544 or other type of deformation formed therein such that upon sealingof the shaped layer 540 to the backing layer 542 a compartment is formedfor holding or containing the medical device product 512. The productcompartment 544 may be accessed by removing the backing layer 542 fromthe package 520 to expose the compartment 544 and the medical deviceproduct 512 held therein. In some embodiments, an edge portion of thebacking layer is configured to not adhere to the shaped layer 540, so asto simplify tearing of the backing layer off the shaped layer. In otherembodiments, a starting notch may be provided to facilitate tearing theedge of the protective package toward the compartment.

The shaped layer 540 and the backing layer 542 may be sealed together,such as by conduction or any sealing method known in the art, to preventready access to the medical device product 512 held therein. In someembodiments, a hermetic seal is formed. The shaped layer 540 may beformed from any of a variety of rupture-resistant, semi-rigid material.Any thermoformed material used in blister packaging, such as plastic,may be used. Materials that may be used to form the shaped layer includepolyvinyl chloride, polyethylene, polyethylene terephthalate,polyethylene terephthalate glycol, polyvinylidene chloride,polypropylene, polyethylene, styrene, copolymers or combinationsthereof, or other suitable materials for packaging. The material may bea single ply or multiple plies or laminations. The material may be amolded part and be selected to retain a desired shape and to be crushresistant so that the medical device product within the compartment isretained therein without being damaged. If viewing of the medical deviceproduct 512 within the product compartment 544 is desirable, then atransparent material may be used. Compatibility of a blister materialwith the product to be contained within the compartment may be animportant factor in selection of a material for the shaped layer. Inaddition, the blister material is preferably formed of a material thatensures stability even when exposed to certain sterilization techniques(e.g., electronic beam sterilization or other light-based sterilizationmethods), such that it does not sustain damage or undergo an alterationthat may result in structural weakening.

The shaped layer 540 is preferably formed with a contour thatsubstantially corresponds to the shape of the medical device product512. To ensure that the medical device product 512 is secured in a fixedposition and fixed orientation within the protective package 520, theshaped layer 540 may include a region that is shaped and dimensioned tocontact and grip or hold a region (e.g., a rigid portion not affected bycontact) of the medical device product. In some embodiments, the shapedlayer 540 is designed to grip only one region of the medical deviceproduct 512. However, in other embodiments, the shaped layer 540 isdesigned to contact and grip a plurality of regions of the medicaldevice product 512 to provide additional securement of the medicaldevice product. In these embodiments, the plurality of contact regionsare discontinuous and not joined with each other. Generally, the contactregion(s) of the shaped layer are designed to contact region(s) of themedical device product not sensitive to touch. For example, the contactregion of the shaped layer may be designed to grasp regions of thesensor insertion device or the on-skin electronics housing unit, insteadof the glucose sensor which is highly susceptible to damage from contactwith other objects. As illustrated in FIG. 5B, in some embodiments, theshaped layer 540 comprises a shaped portions or latches 572, 574 thatare designed to securely engage notches 372, 374 (see in FIGS. 3B-3E),such that such that movement of the protective package and/or thesecondary container does not result in a shift in the position ororientation of the sensor insertion device relative to the protectivepackage. It is contemplated that the shaped portions or latches may beof any of a variety of shapes and dimensions, as long as they serve tosecure the product held in the protective package.

It has been found that the adhesive patch 382 (see FIG. 3B) which formsa part of the electronic housing unit is more susceptible to earlypeel-off from a wearer's skin (and thus a shorter usable lifetime) ifthe adhesive patch has been folded prior to use. To overcome this issue,in some embodiments, the shaped layer is formed with a contour thatprevents contact between it and the adhesive patch. The contour may beshaped and dimensioned to discourage a user from removing the product bytugging or pulling on certain components that can be unintentionallydetached prior to the proper time for detachment. For example, thesafety lock 392, 592 of the product 512 can inadvertently becomedetached as the user tries to remove the product 512 from the protectivepackage. To minimize this risk, in one embodiment, the contour of theshaped layer covering the safety lock 392, 592 is shaped to not allowfor much space for a finger that a user would have to use to remove theproduct 512 from the protective package. This general design concept isalso applicable to other components in which it is desirable to preventinadvertent or unintentional detachment. To minimize the risk of theinadvertent detachment and to facilitate safe removal of the product, asillustrated in FIG. 5B, the shaped layer may designed with an portion582 shaped and dimensioned to allow a user's finger to safely pull outand remove the product 512 at a portion of the product 512 that is notsensitive to touch and not likely to detach.

The backing layer 542 may be formed from a rupture and punctureresistant material, such as a tear-resistant lamination. The material ofblister backing layer may be selected to be compatible with the materialof the shaped layer, such as for heat sealability. Additionally, as withthe shaped layer, compatibility of the shaped layer material with themedical device product to be contained within the compartment 544,barrier properties, such as, but not limited to, those that wouldcontribute to stability of the product, may be important considerationsin selecting the material of the backing layer 542. Moreover, in certainembodiments, the material may be designed to be impermeable tomicroorganisms, but permeable to moisture vapor and sterilant gas (e.g.,ethylene oxide, hydrogen peroxide[1] and ozone), if a sterilant gastechnique is employed in replacement of (or in addition to) alight-based sterilization technique. Exemplary materials that may beused for the backing layer include, without limitation, polyvinylchloride, polyvinylidenechloride, polyacrylonitrile, polyethylene (e.g.,a high-density polyethylene fiber, such as, DuPont™ Tyvek®),polyethylene terephthalate, polyethylene naphthalate, polypropylene,polyacrylate, cyclic olefins, polystyrene, polyesters, polyamides,ethylene vinyl alcohol, polyvinyl alcohol, and copolymers thereof; andpaper. Similar to the shaped layer, the backing layer material ispreferably formed of a material that permits exposure to certainsterilization techniques (e.g., electronic beam sterilization or otherlight-based sterilization methods or sterilant gas methods) withoutsustaining damage or undergoing an alteration that may result in damageto the medical device product.

In some embodiments, the protective package may be configured to beimpermeable to water vapor and/or oxygen, so as to permit certaincontrol of the atmospheric environment defined by the sealedcompartment. A protective package of this type would be suitable forapplications designed for medical devices that have a moisture-sensitiveor oxygen-sensitive component, for example, a component made of apolymer which is subject to hydrolytic degradation and/or a componentthat undesirably undergoes a change in a certain property (e.g.,sensitivity to glucose) when exposed to changes in moisture. For theseapplications, a material permeable to moisture and/or oxygen exchange(e.g., a high-density polyethylene fiber, such as, DuPont™ Tyvek®) wouldnot be used. Instead, to avoid undesirable chemical reactions related tooxidation and hydrolysis reactions with the oxygen and/or moisture inair, materials that are impermeable to moisture vapor and/or oxygenwould be used. These materials include, without limitation, certainpolymers or plastic foil comprised of polyethylene, polypropylene,polyvinyl chloride, or any other types of plastic foils, or metal sheetssuch as aluminum foil, or any combinations thereof.

The backing layer 542 may be imprinted with information relating to themedical device product. The information may include a lot numbercorresponding to the manufacturing of the medical device product toaccount for potential lot-to-lot variations sensors to ensure accuratesensor results. In some embodiments, the backing layer 542 includesinformation that facilitates calibration of the sensor.

In some embodiments, the protective package 520 may be designed suchthat the backing layer contacts the medical device product at one ormore regions. This contact may be in addition to any contact providedbetween the shaped layer and the medical device product. Like the shapedlayer, the contact region(s) of the backing layer are designed tocontact region(s) of the medical device product not sensitive to touch.FIG. 5C provides a perspective view of the protective package of FIG. 5Aafter it has been assembled and sealed.

Referring back to FIG. 4, the packaging system 400 also includes asecondary container 410 and a retainer 430 or tray shaped anddimensioned to secure one or more protective packages 420, 520 in afixed position and fixed orientation within the secondary container 410.To provide this securement, the retainer 430 includes cut-outs shapedand dimensioned to conform to certain portions of the shaped layer. Inthe embodiment shown, the retainer 430 is a piece that is inserted intothe secondary container 410. As illustrated in FIG. 6, which provides aclose-view of the retainer 630, the retainer 630 includes a base 664 anda plurality of side walls 668 comprising the cut-outs 662. Each of theside walls 668 includes a ledge 670 that allows the protective packageto be placed thereon. As illustrated, a pair of cut-outs 662 may beformed to accommodate different regions of a protective package's shapedlayer. Accordingly, in this embodiment, each pair of cut-outsfacilitates the securement of one protective package. The retainer 630may include any number of cut-out pairs. In some embodiments, theretainer includes one pair of cut-outs to accommodate one protectivepackage. However, in other embodiments, the retainer may include a two,three, four (as illustrated), five, six, nine, ten, twelve, sixteen, ormore cut-out pairs to accommodate a corresponding number of protectivepackages. Along each of the side walls, the cut-outs are formed to besubstantially evenly spaced apart from each other. Because of thesubstantially even spacing, each of the protective packages and theproduct contained therein are also substantially evenly spaced apartfrom each other. This arrangement permits each of the protectivepackages (and the medical device products contained therein) to receivesubstantially equal dosages of radiation during sterilization.

The base 664 and the plurality of side walls 668 are shaped anddimensioned to fit securely in the secondary container, such thatmovement of the secondary container 410 does not result in movement ofthe retainer 430, 630 therein. In turn, because of the securementprovided by the retainer 430, 630 movement of the second container 410does not result in movement of the protective package 420 and themedical device product disposed therein, relative to secondary container410. In alternative embodiments, the retainer may be integral with thesecondary container, such that the side walls of the secondary containerare have cutouts formed thereto.

In some embodiments, the packaging system also includes a thirdcontainer shaped and dimensioned to secure one or more second containersin a fixed position and fixed orientation within the third container410. In certain embodiments, the third container is dimensioned andconfigured to hold only one level of a plurality of second containers.In other words, there are no second containers that are stacked on eachother. By preventing stacking, the packaging system eliminates the riskof a shadow effect in which a container (holding a product) stacked ontop of another container (also holding a product) blocks or reduces theamount of radiation from the E-beam apparatus from reaching the lowercontainer, thereby resulting in unequal radiation dosage received by theproducts.

RFID (Radio Frequency Identification) technology may also be used to tagand trace products through the production and distribution chain. AnRFID tag can be written or coded with specific manufacturinginformation, such as lot number, expiration date, final release status,etc., and then be used to communicate for tracking or data collection.Sometimes, RFID tags are used in packaging materials. RFID chips mayrely on E²PROM (Electrically Erasable Programmable Read-Only Memory) fordata storage. It has been found, however, that this type of memory isunable to maintain data integrity when exposed to irradiation at thelevels typically required to sterilize medical devices using E-beamradiation in certain implementations. It has been unexpectedly foundthat FRAM (Ferroelectric Random Access Memory), a newly developed RFIDtechnology, maintains data integrity even after exposure to a dose of 50kGray radiation from an E-beam sterilization apparatus.

In some embodiments, one or more components of the sensor system and/ora portion of the packaging system incorporates an FRAM RFID chip. TheFRAM RFID chip can be applied (e.g., adhered) to the outer surface of aglucose sensor system component(s) or packaging. Alternatively oradditionally, the FRAM RFID chip can also be incorporated (e.g., molded)into the component or packaging. By incorporating the use of an FRAMRFID chip into the sensor system and/or the packaging system, the sensorsystem can then be sterilized through an E-beam (or otherradiation-based) sterilization process performed at higher radiationlevel (e.g., at or greater than 50 kGray) than one that would typicallydamage conventional memory chips. It is contemplated that an FRAM RFIDchip or any other memory chip capable of withstanding high radiationlevels and maintaining data integrity after exposure to a dose ofradiation (e.g., E-beam radiation) of 50 kGray for 30 seconds or more(e.g., 1 minute, 2 minutes, 3 minutes, 5 minutes, or 10 minutes) may beapplied or incorporated into any portion of the packaging system and anycomponent of the sensor system.

Method

Medical devices in many cases have to undergo sterilization prior to useby a patient. After sterilization, the protective package prevents themedical device product from containment. A sterile product is one whichis free of viable microorganisms. The International Standards forsterilization of medical devices require, when it is necessary to supplya sterile product item, that adventitious microbiological contaminationof a medical device from all sources be minimized by all practicalmeans. Even so, product items produced under standard manufacturingconditions in accordance with the requirements for quality managementsystems for medical devices may, prior to sterilization, havemicroorganisms on them, albeit in low numbers. Such products arenon-sterile. The purpose of sterilization processing is to inactivatethe microbiological contaminants and thereby transform the non-sterileitems into sterile ones.

Because of the package design disclosed herein, the medical deviceproducts held within the package are substantially prevented fromshifting to different positions and/or orientations within the packageprior to and during sterilization. Thus, during sterilization, theimplantable analyte sensors each receive different amounts of radiationand a different radiation profile. This difference in radiation dosagemay result in inconsistent sensor properties and thus inconsistentsensor performance among sensors. Accordingly, it is desirable topackage the sensors in a manner that prevents or substantially inhibitssensor movement within the package. It is also desirable to sterilizethe sensors in a manner that permits consistency in radiation dosagereceived and consistency in radiation profile.

With reference to FIG. 7, one embodiment of a method for sterilizing amedical device product comprises the following steps. In Box 710, anoperator places and secures the medical device product (e.g., acontinuous glucose sensor, an electronics housing unit, and/or an sensorinsertion devices) into a compartment of the shaped layer in a mannersuch that a region of the shaped layer engages and grasps acorresponding region of the medical device product. Securement resultsin the medical device product being in a fixed position and fixedorientation within the protective package such that movement of theprotective package does not result in shifting of the position ororientation of the medical device product therein. Next, in Box 720 thebacking layer and the shaped layer are joined together by any sealingmethod known in the art that adequately seals the medical device productwithin the compartment. Exemplary sealing methods include heat sealing,adhesive seals (such as with heat-activated or solvent adhesive), RF orsonic seals, or any other suitable means. In some embodiments, thematerials of the shaped layer and/or the backing layer may bepre-treated to facilitate sealing of such materials together. Forinstance, a coating may be applied to either or both materials to permitheat sealing. Through the above-described process, a protective packageis formed, whereby the medical device product is secured therein andprevented from shifting its position or orientation relative toprotective package. This process may be repeated to form a plurality ofprotective packages, each of which secures at least one medical deviceproduct.

In some embodiments, prior to sealing of the shaped layer to the backinglayer, an inert gas is introduced to the compartment to control, reduce,and/or eliminate the oxygen content and/or moisture content in thecompartment. Without being bound by theory, it is believed that theintroduction of inert gas would substantially force all of the ambientair away from the entire surface area of the medical device product.Inert gases that may be used include, without limitation, nitrogen andnoble gases (e.g., argon) may be used. In some embodiments, the inertgas is heavier than air, thereby allowing the inert gas injected todisplace the ambient air surrounding the medical device product andpurge the air away from the medical device product. In certainembodiments, to even further ensure that minimal or no ambient airremains in the compartment, prior to the introduction of the inert gas,the compartment undergoes vacuuming to remove ambient therefrom.

In Box 730, the protective package is placed onto the retainer andsecured by making sure that the cut-outs of the retainer are engagedwith corresponding regions of the shaped layer. This step may berepeated with packages designed to hold and secure a plurality ofprotective packages. In such situations, in accordance with Box 740,confirmation is made to ensure each of the plurality of protectivepackages (and the medical device products contained therein) are alignedin uniform orientation and each are spaced substantially equally apartwithin the secondary container. Thereafter, the lid of the secondarycontainer is closed, and in Box 750, the second container is moved to asterilization apparatus.

Sterilization may be performed by any of a variety of techniques. Insome embodiments, sterilization is performed by light-based techniques(e.g., techniques utilizing gamma rays or x-rays). In furtherembodiments, an e-beam sterilization process is used in which themedical device product is transported via a conveyor system into ashielded booth where it is scanned. In certain embodiments, thepackaging system that the sensors are contained in during sterilizationis used for shipping the sensors to patients for use. In alternativeembodiments, sterilization is performed by sterilant gas methods.

In some embodiments, the packaging system is interactive and employsvisual and/or audio features designed to help the user understand how touse the glucose sensor system. FIG. 8 illustrates one embodiment of apackaging system 800 with various components of the sensor system placedtherein. As illustrated, components of the sensor system (e.g., thetransmitter 802, the applicator 804, the receiver 806) are assigned tocertain compartments 820, 840, 860 of the packaging system in which thecompartments 820, 840, 860 are readily identifiable through certainvisual characteristics (e.g., color coding 822, 842, 862 and/or numbercoding). During system setup, a video, pictures, and/or illustrationsare shown to the user to provide a step-by-step tutorial on how to useglucose sensor system. The video, pictures, and/or illustrations may beprovided with audio which describes the steps involved in the setupprocess. The videos, pictures, and/or illustrations may be played usingany of a variety of electronic devices with a display, such as, forexample, a receiver provided in the package, a smartphone, a computer,and/or a tablet.

The packaging (e.g., through use of a label on the packaging) or anarticle inside the packaging (e.g., a user manual 850) can be used toprovide information for downloading an app (e.g., to a smartphone) orsoftware (e.g. to a computer), so that the user can obtain and play thevideo on the receiver, smartphone, computer, or any other electronicdevices capable of playing videos. The app or software may work inconcert with the user manual 850 and/or packaging, which together aredesigned to provide the user with a cohesive, unified experience ofunboxing and setting up the sensor system. For example, the cohesive,unified experience may include walking the user through a bluetoothpairing process (or any other step) using videos, pictures, orillustrations while the directions are audibly communicated to the user.

In certain embodiments, the packaging system employs near fieldcommunication (NFC) and/or other scanning technologies (e.g.,technologies involving image or barcode scanning) to improve theexperience of unboxing and setting up the sensor system. For example,the packaging system may include certain defined zones that can beidentified by instructions, which can be number-coded and/orcolor-coded. For example, as illustrated in FIG. 8, the packaging system800 has a zone 870 that has a barcode or image (not shown) for scanningand that is identified by an instruction (e.g., “Place Phone Here”). Byfollowing the instruction and thereby placing the phone in thatparticular zone, the phone is then enabled to read the code instantlyusing NFC or other scanning technologies, thereby eliminating the needfor a user to manually enter a code. Instructions like these and theschemes used to make them readily identifiable to the user help avoidpotential confusion.

In the embodiment illustrated in FIG. 8, the box employs color-codingand numbering that correspond to the various steps of the setup process.The same color-coding scheme may also be applied to the instructionmanual. For example, the section of the user manual that correspond toStep 1 may have page edges (or entire pages) that have the same color asthe zone 890 and compartment 820 corresponding to Step 1.

It has also been found that many users no longer desire tangibleinstruction guides, such as the traditional instruction guides in theform of a paper book. Indeed, tangible instruction guides may be morecostly, yet less useful and less instructive than a digital version ofan instruction guide, in particular if the digital version isinteractive and easy for the user to navigate. In some implementationswhere a smart phone is used to download a glucose monitoring app and runthe app, as described above, the initial download or launch of the appautomatically triggers the phone to prompt the user as to whether theuser would like to download a digital version of an instruction guide.If the user confirms that he or she would like to download the digitalinstruction guide, then the phone automatically requests a copy from aremote server with access to the instruction guide, which may be thesame remote server that provides the app or a remote server associatedwith the manufacturer of the glucose monitoring system, for example. Theinstruction guide may then be accessed through the glucose monitoringapplication or through a third party application that is used to accessand organize digital books, such as so-called digital libraries.

To illustrate the above, the following is one specific implementation ofdownloading and accessing a digital instruction guide. In thisimplementation, the user's phone is an iPhone available from Apple,Inc., and the user downloads a continuous glucose monitoring (CGM) appusing the iPhone from Apple Inc.'s App Store. Once the CGM applicationis downloaded, the user launches the application by selecting an icondisplayed on the display screen of the iPhone. Upon launch, the CGMapplication causes the iPhone to trigger a pop-up prompt asking the userif the user would like to download the instruction manual to the iPhone.The download can be to a digital library, for example, Apple's iBooksdigital library application. If the user confirms downloading theinstruction manual, then the instruction manual is downloaded from aremote server, such as a server operated by Apple, Inc. and associatedwith iBooks, for example. Once downloaded, the user can launch theiBooks application and access the user instruction guide.

Kits

Kits are provided for monitoring continuously monitoring an analyte. Thekits include a packaged product that is a combination of implantableanalyte sensors, an electronics housing unit, a sensor insertion devicefor inserting the implantable analyte sensor into a host, and/orinstructions for using the medical device product. The packaged sensorsare in placed in protective packages, which are secured to a containerby a retainer, such that the packaged sensors are aligned in uniformorientation and secured to prevent shifts in position or orientationrelative to the package.

The above description presents the best mode contemplated for carryingout the present invention, and of the manner and process of practicingit, in such full, clear, concise, and exact terms as to enable anyperson skilled in the art to which they pertain to practice thisinvention. This invention is, however, susceptible to modifications andalternate constructions from those discussed above that are fullyequivalent. Consequently, this invention is not limited to theparticular embodiments disclosed. On the contrary, this invention coversall modifications and alternate constructions coming within the spiritand scope of the invention as generally expressed by the followingclaims, which particularly point out and distinctly claim the subjectmatter of the invention.

All references cited herein, including but not limited to published andunpublished applications, patents, and literature references, areincorporated herein by reference in their entirety and are hereby made apart of this specification. To the extent publications and patents orpatent applications incorporated by reference contradict the disclosurecontained in the specification, the specification is intended tosupersede and/or take precedence over any such contradictory material.

It should be understood that the methods described in this document aremerely examples, and some steps may be omitted or replaced by othersteps. Furthermore, although the steps of the method are described in aparticular order, the various steps need not be performed sequentiallyor in the order described.

Terms and phrases used in this document, and variations thereof, unlessotherwise expressly stated, should be construed as open ended as opposedto limiting. As examples of the foregoing, the term ‘including’ shouldbe read to mean ‘including, without limitation’ or the like; the term‘comprising’ as used herein is synonymous with ‘including,’‘containing,’ or ‘characterized by,’ and is inclusive or open-ended anddoes not exclude additional, unrecited elements or method steps; theterm ‘example’ is used to provide instances of the item in discussion,not an exhaustive or limiting list thereof; and adjectives such as‘known’, ‘normal’, ‘standard’, and terms of similar meaning should notbe construed as limiting the item described to a given time period or toan item available as of a given time, but instead should be read toencompass known, normal, or standard technologies that may be availableor known now or at any time in the future. Likewise, a group of itemslinked with the conjunction ‘and’ should not be read as requiring thateach and every one of those items be present in the grouping, but rathershould be read as ‘and/or’ unless expressly stated otherwise. Similarly,a group of items linked with the conjunction ‘or’ should not be read asrequiring mutual exclusivity among that group, but rather should be readas ‘and/or’ unless expressly stated otherwise. In addition, as used inthis application, the products ‘a’ and ‘an’ should be construed asreferring to one or more than one (i.e., to at least one) of thegrammatical objects of the product. By way of example, ‘an element’means one element or more than one element.

What is claimed is:
 1. A package for receiving and securing a product,the package comprising: at least one product, each product comprising:an on-skin assembly comprising an adhesive patch configured to adhere toa host's skin; a transcutaneous glucose sensor operably connected to theon-skin assembly, wherein the glucose sensor comprises an electrodesurrounded by a membrane configured to be exposed to interstitial fluid;at least one first container configured to receive and secure the atleast one product therein, wherein the at least first container isconfigured to be permeable to water vapor; a second container configuredto receive the at least one first container; and a retainer configuredto secure the at least one first container in a fixed position and fixedorientation within the second container such that movement of the secondcontainer does not result in substantial movement of the first containerwithin the second container.
 2. The package of claim 1, wherein the atleast one first container comprises a plurality of first containers,wherein the retainer comprises a plurality of regions each configured tosecure one of the plurality of first containers.
 3. The package of claim2, wherein the plurality of regions of the retainer are spaced apart atan equal distance such that the plurality of first containers are spacedapart at an equal distance.
 4. The package of claim 2, wherein the atleast one product comprises a plurality of products, wherein theplurality of products are aligned in a uniform orientation.
 5. Thepackage of claim 1, wherein the retainer is an integral component of thesecond container.
 6. The package of claim 1, wherein the retainer is aninsert releasably attached to the second container.
 7. The package ofclaim 6, wherein the retainer comprises an aperture or pocket shaped toreceive and conform to a region of the first container.
 8. The packageof claim 1, wherein the on-skin assembly further comprises a housingconfigured to receive an electronics unit.
 9. The package of claim 8,wherein the at least one product further comprises an insertion deviceconfigured to insert the glucose sensor into a host.
 10. The package ofclaim 1, wherein the at least one first container comprises a shapedlayer and a backing layer adhered to the shaped layer.
 11. The packageof claim 10, wherein the backing layer comprises: a material selectedfrom the group consisting of polyvinyl chloride, polyvinylidenechloride,polyacrylonitrile, polyethylene, polyethylene terephthalate,polyethylene naphthalate, polypropylene, polyacrylate, cyclic olefins,polystyrene, polyesters, polyamides, ethylene vinyl alcohol, polyvinylalcohol, and copolymers thereof; and paper.
 12. The package of claim 10,wherein the shaped layer is a molded part with a chamber for receivingthe at least one product.
 13. The package of claim 10, wherein theshaped layer is formed of a film.
 14. The package of claim 13, whereinthe film comprises a polymer selected from the group consisting ofpolyvinyl chloride, polyethylene, polyethylene terephthalate,polyethylene terephthalate glycol, polyvinylidene chloride,polypropylene, polyethylene, styrene, and copolymers thereof.
 15. Thepackage of claim 10, wherein the shaped layer comprises at least oneregion configured to secure the at least one product in a fixed positionand fixed orientation within the at least one first container such thatmovement of the at least one first container or the second containerdoes not result in substantial movement of the at least one productwithin the at least one first container.
 16. The package of claim 15,wherein the at least one region of the shaped layer comprises aplurality of regions configured to secure the at least one product in afixed position and fixed orientation within the at least one firstcontainer.
 17. The package of claim 10, wherein the shaped layer isshaped and dimensioned to prevent bending of the adhesive patch.
 18. Thepackage of claim 1, further comprising a third container, wherein thethird container is dimensioned and configured to receive a plurality ofsecond containers and secure the plurality of second containers in afixed position and fixed orientation.
 19. The package of claim 1,further comprising a third container, wherein the third container isdimensioned and configured to hold only one level of a plurality ofsecond containers.
 20. The package of claim 1, wherein the glucosesensor is sterilized.